Timing of Midazolam and Propofol Administration for Co-Induction of Anaesthesia

Abstract

We aimed to determine the optimum timing of midazolam administration prior to propofol to achieve the maximal reduction in the dose of propofol required to induce anaesthesia. Female (ASA 1-2) patients, aged 18 to 45 years, weighing 40 to 75 kg and scheduled for gynaecological surgery were eligible for the study. Consenting patients were randomly assigned to six groups. Group 1 received saline and Groups 2 to 6 received midazolam 3 mg at 1, 2, 4, 6 or 10 minutes respectively prior to propofol (n=20 to 22 per group) in a blinded manner. Propofol was administered IV over 10 seconds and flushed in with saline 5 ml. Two minutes later, the patient's response to pressure applied to the finger was determined as an index of loss of consciousness. The ED50 of propofol in each group was determined by the up-and-down method. Propofol ED50 was reduced to 34 to 67% (P<0.001) in the midazolam treated groups. There was no significant (P=0.14) difference in propofol ED50 among the five groups which received midazolam. Patients who received midazolam had less recollection of events surrounding induction (P<0.001) and recalled the induction experience as being more pleasant (P=0.03) than those who did not receive midazolam. These results indicate that midazolam may be given up to 10 minutes prior to propofol and still achieve a substantial dose reduction.

Prevention of pain on injection of propofol: systematic review and meta-analysis

“…The primary outcome was the number of patients reporting any pain Studies excluded (n=106): Reviews (n=7) 1 3 4 14-17 Animal studies (n=2) 18 19 Not randomised controlled trials (n=15) [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Improper assessment of pain (n=7) [35][36][37][38][39][40][41] Duplicate publication (n=2) 42 43 Methodological concerns (n=15) [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] Did not measure pain from propofol injection (n=20) [60][61][62][63][64][65][66][67][68]…”

“…Thus, 283 studies were retrieved as potential clinical trials for further evaluation. A further 106 studies were excluded for the following reasons: reviews (seven studies), 1 3 4 14-17 not carried out in humans (n=2), 18 19 not randomised controlled trials (n=15), 20-34 improper assessment of pain (n=7), [35][36][37][38][39][40][41] duplicate publication (n=2), 42 43 methodological concerns (n=15), [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] did not measure pain on injection of propofol (n=20), [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79] intervention not aimed at pain reduction on injection of propofol (n=3), [80][81][82] incomplete data or inability to extract data (...…”

Preoperative Intravenous Midazolam

“…2 In my experience, patients do not recall the burning sensation of a propofol induction to the same degree as seen with unpremedicated patients. This article concurs with a recent meta-analysis 1 that demonstrates no significant effect between benzodiazepine premedication and delayed discharge.…”

A Comparative Study of Small Dose Ketamine, Midazolam and Propofol as Co-Induction Agent to Propofol

“…Predosing and co-induction both reduce the dose of induction agent required to achieve hypnosis and any form of premedication is likely to have similar effect (2,12,13) Many previous authors have reported reduced dose requirement of propofol following pre-administration of midazolam (2,4,5,14) ketamine (6,7,11) or propofol (l, 3,8) with or without fentanyl. Anderson and Robb (1998) proposed a pharmacokinetic theory that part of the mechanism of action of co-induction drugs is to reduce anxiety and the associated sympathetic response.…”